DESCRIPTION: Understanding the acute and chronic response of muscle respiration during exercise is an important step in the development of effective methods for promoting fitness for all Americans. The goal of this research is to define the mechanisms that control and link in vivo energy dynamics in skeletal muscle to those of the whole organism. Our central hypothesis is that muscle fiber type heterogeneity is an important determinant of the metabolic and gas exchange responses to exercise. Critical to our growth in understanding these processes is the comparison of predictions and insights gained from isolated systems such as mitochondria and muscles to the responses of the intact organism. The aims of this proposal are to answer these fundamental questions: 1. Do the models of respiratory control proposed from muscle or mitochondria studies (Pcr, ADP, DGATP) adequately describe respiratory adjustments to exercise in human mixed muscles? 2. What role does muscle fiber type heterogeneity play in the metabolic response to exercise? To the adaptations to endurance exercise training? 3. What information can we learn regarding control of skeletal muscle respiration from whole body gas exchange responses during exercise? To answer these questions, studies are designed which combine 31P magnetic resonance spectroscopy (MRS) of muscle phosphagens with measurement of breath-by-breath gas exchange during exercise. Protocols include hypoxia, b-blockade, acidosis and endurance training in subjects with diverse fiber types to distinguish between models of respiratory control and to define the role of fiber type in exercise energetics. This project will provide fundamental information critical to our long-range goals of a) understanding and differentiating the effects of cardiovascular, pulmonary or muscle disease from those of simple deconditioning on muscle and whole-body respiration, and b) developing sound rehabilitation strategies to improve exercise tolerance in patients.